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Abstract：
Leishmania is the causative agent of cutaneous and visceral diseases affecting millions of individuals worldwide. Pseudouridine (Ψ), the most abundant modification on rRNA, changes during the parasite life cycle. Alterations in the level of a specific Ψ in helix 69 (H69) affected ribosome function. To decipher the molecular mechanism of this phenotype, we determine the structure of ribosomes lacking the single Ψ and its parental strain at ∼2.4-3 Å resolution using cryo-EM. Our findings demonstrate the significance of a single Ψ on H69 to its structure and the importance for its interactions with helix 44 and specific tRNAs. Our study suggests that rRNA modification affects translation of mRNAs carrying codon bias due to selective accommodation of tRNAs by the ribosome. Based on the high-resolution structures, we propose a mechanism explaining how the ribosome selects specific tRNAs.
摘要：
利什曼原虫是影响全世界数百万人的皮肤和内脏疾病的病原体。伪尿苷(Φ),rRNA上最丰富的修饰，寄生虫生命周期中的变化。螺旋69（H69）中特定的Φ水平的变化会影响核糖体功能。为了破译这种表型的分子机制，我们使用cryo-EM在〜2.4-3µ分辨率下确定了缺乏单个Φ及其亲本菌株的核糖体的结构。我们的发现证明了H69上的单个Φ对其结构的重要性以及其与螺旋44和特定tRNA相互作用的重要性。我们的研究表明，由于核糖体对tRNA的选择性调节，rRNA修饰会影响携带密码子偏倚的mRNA的翻译。基于高分辨率结构，我们提出了一种解释核糖体如何选择特定tRNA的机制。
